Research in the Toxicology Center at the University of Iowa will center on mechanisms related to the toxicity of substances used as drugs or environmental agents. Mechanisms of toxicity will be studied. Understanding of the toxicity of substances such as cobalt, lead and certain antibiotics such as adriamycin will be sought in isolated perfused rat hearts. Localization of drug metabolizing enzymes in liver and other tissue will be determined in normal and xenobiotic-treated animals. Various toxic substances will be employed in order to determine differential effects on localization of enzymes in the liver lobule. The effect of agents on endoplasmic reticulum membrane will be studied as will agents which affect pulmonary biochemistry and physiology. The regulation of oxygen toxicity and the understanding of substances which may enhance or protect the lungs of newborn and adult animals are under investigation. The mechanisms of islet cell toxicity produced by agents such as alloxan and cyproheptadine will be evaluated.